Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo

M J Farthing , G P Vinson , C R Edwards

Gut +

|

March 1, 1982

View abstract on PubMed

Summary

The gastrointestinal tract significantly metabolizes testosterone into weaker androgens. This gut metabolism, not the liver, likely explains why oral testosterone is ineffective for hormone replacement therapy.

Area Of Science

Endocrinology
Gastroenterology
Pharmacology

Background

The jejunal mucosa possesses a significant capacity to oxidize testosterone to androstenedione via 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD).
Previous studies established considerable 17 beta-HSD activity in the jejunum.

Purpose Of The Study

To measure 17 beta-HSD activity across various gastrointestinal regions.
To investigate testosterone metabolism in rat jejunum using in vitro preparations (slices and everted sacs).
To estimate the in vivo contribution of intestinal testosterone metabolites to circulating androgens via rat portal vein sampling.

Main Methods

Assessed 17 beta-HSD activity in homogenates from gastric, duodenal, jejunal, ileal, and colonic mucosa.
Incubated rat jejunal slices and everted sacs with testosterone to identify metabolites.
Collected portal vein blood from rats to measure androgen levels and metabolites in vivo.

Main Results

17 beta-HSD activity was highest in gastric and duodenal mucosa, also detected in jejunum, ileum, and colon.
In vitro, jejunal preparations produced androstenedione and other metabolites, potentially including dihydrotestosterone.
In vivo, androstenedione was the predominant metabolite in portal vein blood, consistent with mucosal homogenate findings.

Conclusions

Testosterone oxidation is the primary metabolic pathway in the intestinal mucosa.
The gastrointestinal tract has a substantial capacity to reduce testosterone's potency.
Gut metabolism, rather than hepatic, is likely responsible for the ineffectiveness of oral testosterone replacement therapy.

Related Concept Videos